Banerjee Subham, Chattopadhyay Pronobesh, Ghosh Animesh, Bhatnagar Aseem, Veer Vijay
Division of Pharmaceutical Technology, Defence Research Laboratory, Post Bag No: 2, Tezpur, 784 001, Assam, India.
Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, 835 215, Jharkhand, India.
Eur J Drug Metab Pharmacokinet. 2016 Jun;41(3):219-30. doi: 10.1007/s13318-014-0250-5. Epub 2014 Dec 30.
In the present study, a simple reverse-phase high-performance liquid chromatography method with diode array detection has been developed and validated for the simultaneous determination and quantification of eserine and pralidoxime chloride in rabbit plasma and its application to pharmacokinetic study. The pharmacokinetic study was performed after transdermal application of single patch in rabbits. The plasma levels of both drugs following transdermal application of single patch were maintained for 72 h after removal of the patch. The maximal concentrations (C max) of both drugs were significantly reduced while the mean areas under the plasma concentration vs. time moment curve and mean residence times were evidently increased and extended, respectively. A sustained activity was observed over a period of 3 days. This sustained activity was due to the controlled release of drug into the systemic circulation following transdermal application. Linear correlation was also observed when fraction of drug permeated was correlated with the fraction of drug absorbed at the same time point. Gamma scintigraphy imaging on rabbit following transdermal patch application was performed to ascertain the localization of drugs in rabbit brain.
在本研究中，已开发并验证了一种采用二极管阵列检测的简单反相高效液相色谱法，用于同时测定和定量兔血浆中的毒扁豆碱和氯解磷定，并将其应用于药代动力学研究。药代动力学研究是在兔经皮应用单个贴片后进行的。在去除贴片后，经皮应用单个贴片后两种药物的血浆水平维持了72小时。两种药物的最大浓度（Cmax）显著降低，而血浆浓度-时间曲线下的平均面积和平均驻留时间分别明显增加和延长。观察到持续3天的持续活性。这种持续活性是由于经皮应用后药物向体循环的控释所致。当同时将药物渗透分数与药物吸收分数相关联时，也观察到线性相关性。对经皮贴片应用后的兔进行γ闪烁显像，以确定药物在兔脑中的定位。
